Fluctuations of cell population in a colonic crypt.

Abstract

The number of stem cells in a colonic crypt is often very small, which leads to large intrinsic fluctuations in the cell population. Based on the model of cell population dynamics with linear feedback in a colonic crypt, we present a stochastic dynamics of the cell population [including stem cells (SCs), transit amplifying cells (TACs), and fully differentiated cells (FDCs)]. The Fano factor, covariance, and susceptibility formulas of the cell population around the steady state are derived by using the Langevin theory. In the range of physiologically reasonable parameter values, it is found that the stationary populations of TACs and FDCs exhibit an approximately threshold behavior as a function of the net growth rate of TACs, and the reproductions of TACs and FDCs can be classified into three regimens: controlled, crossover, and uncontrolled. With the increasing of the net growth rate of TACs, there is a maximum of the relative intrinsic fluctuations (i.e., the Fano factors) of TACs and FDCs in the crossover region. For a fixed differentiation rate and the net growth rate of SCs, the covariance of fluctuations between SCs and TACs has a maximum in the crossover region. However, the susceptibilities of both TACs and FDCs to the net growth rate of TACs have a minimum in the crossover region.